Purpose: The Bastyr University/University of Washington PCCTR Oncomycology Research Center will investigate the immunologic and antitumor effects of Trametes versicolor (Tv) a traditional Chinese medicine medicinal mushroom, for use in the treatment of cancer patients in the US. The past 6 years of research at our NCCAM-funded Developmental Center for Research in CAM (DCRC) led us to conclude that the immunomodulating mushroom Tv, widely used by Japanese oncologists, may be an effective adjunctive immune therapy because of its targeted activation of the innate and adaptive immune system via TOll-lil<e receptors 2 (TLR2). The DCRC identified Polysaccharide Krestin[unreadable] (PSK), manufactured and licensed in Japan as an oncologic therapy Tv product which is IND-ready and suitable for NIH clinical trials. Hypotheses;PSK will enhance tumor immunogenicity in breast cancer patients whose tumors overexpress HER-2/neu, improve the efficacy of trastuzumab (Herceptin[unreadable]) and improve the efficacy of HER-2/neu peptide vaccination. PSK, a TLR2 agonist, will augment innate antitumor immunity in men with prostate cancer. PSK combined with docetaxel, a promoter of the TLR4 pathway, will be safe and will not pharmacologically interact with docetaxel and antitumor immune response will be further enhanced in prostate cancer patients. Goals and Methods: Project 1: Conduct a translational preclinical study in the Her-2/neu mouse model and proceed rapidly to a phase Ii controlled clinical trial of PSK[unreadable] as an oral immune adjuvant co-administered with HER2 vaccination therapy in women with advanced HER-2/neu positive breast cancer (n=30). Project 2: Conduct a pharmacokinetic study and phase I dose escalation trial and pharmacokinetic study of PSK with docetaxel to treat metastatic prostate cancer (n=32). Significance: PSK is a potentially important immune therapy for patients with breast and prostate cancer. Our center has elucidated the TLR mechanism of action and will be the first to conduct clinical trials of PSK in US cancer patients.